Cytochrome P450 OxyBtei Catalyzes the First Phenolic Coupling Step in Teicoplanin Biosynthesis
Cytochrome P450 OxyBtei Catalyzes the First Phenolic Coupling Step in Teicoplanin Biosynthesis
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DOI：
10.1002/cbic.201402441
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发表时间：
2014-12-15
期刊：
影响因子：
3.2
通讯作者：
Cryle, Max J.
中科院分区：
文献类型：
--
作者：
Haslinger, Kristina;Maximowitsch, Egle;Cryle, Max J.
细菌细胞色素P450是氧化血红蛋白P450超家族的一个重要分支，经常参与复杂天然产物的生物合成。那些被称为“氧化酶”亚群的酶在糖肽类抗生素的生物合成中起着至关重要的作用，包括万古霉素和替柯planin。氧化酶催化非核糖体抗生素前体肽中芳香残基的交联，而它仍然与非核糖体肽合成酶（NRPS）结合；这种交联确保了糖肽的三维结构，这对抗生素活性至关重要。我们已经鉴定了OxyB(tei)，这是生物合成中第一个氧化酶。我们的研究结果表明，OxyB（tei）具有与其他Oxy蛋白相似的结构，并且在交联nrps结合的肽底物中具有活性。然而，与研究充分的万古霉素同系物相比，OxyB（tei）对肽底物的活性谱明显改变。
Bacterial cytochrome P450s form a remarkable clade of the P450 superfamily of oxidative hemoproteins, and are often involved in the biosynthesis of complex natural products. Those in a subgroup known as "Oxy enzymes" play a crucial role in the biosynthesis of glycopeptide antibiotics, including vancomycin and teicoplanin. The Oxy enzymes catalyze crosslinking of aromatic residues in the non-ribosomal antibiotic precursor peptide while it remains bound to the non-ribosomal peptide synthetase (NRPS); this crosslinking secures the three-dimensional structure of the glycopeptide, crucial for antibiotic activity. We have characterized OxyB(tei), the first of the Oxy enzymes in teicoplanin biosynthesis. Our results reveal that OxyB(tei) possesses a structure similar to those of other Oxy proteins and is active in crosslinking NRPS-bound peptide substrates. However, OxyB(tei) displays a significantly altered activity spectrum against peptide substrates compared to its well-studied vancomycin homologue.